It is well known that putative Candida albicans virulence factors include adhesins, the secretion of hydrolytic enzymes, cellular morphogenesis, and phenotypic switching. In this chapter, the authors argue in favor of the recent suggestion that virulence factors are expressed at the cell surface and contribute directly to fungus-host interactions. However, the chapter also highlights the importance of C. albicans fitness attributes for virulence. The overall aim must be to increase the precision with which the roles of specific C. albicans virulence and fitness factors can be dissected. If the consequence of virulence is host damage and the aim is to assess the roles of specific molecular virulence factors in inflicting this damage, then experimental models of Candida infection should permit quantification of such damage. The most widely used animal model of hematogenously disseminated Candida infection (candidemia) involves intravenous challenge of mice with an inoculum that is lethal in virulent, wild-type strains. Its scientific advantage is that it offers high reproducibility and is currently by far the most widely used assay of C. albicans virulence. One possible conclusion from the very large numbers of putative virulence factors discovered by gene disruption approaches is that C. albicans is highly susceptible to the consequences of many different gene disruptions. Morphological interchange between yeast, pseudohyphal, and hyphal forms is one of the earliest recognized properties of C. albicans.

Temporal stages of C. albicans infection in a mammalian host. Fungal cells (a) adhere to, and become commensal colonizers of, an epithelial surface (b). Given local deterioration in host defense, the fungi can penetrate epithelial layers (c); they may be able to invade as far as the bloodstream (d), leading to dissemination of fungal propagules, which may adhere to and penetrate vascular endothelia and thus gain access to deep tissues.

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Figure 1.

Temporal stages of C. albicans infection in a mammalian host. Fungal cells (a) adhere to, and become commensal colonizers of, an epithelial surface (b). Given local deterioration in host defense, the fungi can penetrate epithelial layers (c); they may be able to invade as far as the bloodstream (d), leading to dissemination of fungal propagules, which may adhere to and penetrate vascular endothelia and thus gain access to deep tissues.

106. Romani,L.,, F.Bistoni, and, P.Puccetti.2003.Adaptation of Candida albicans to the host environment: the role of morphogenesis in virulence and survival in mammalian hosts.Curr. Opin. Microbiol.6:338– 343.

127. Sundstrom,P.,, J. E.Cutler, and, J. F.Staab.2002.Reevaluation of the role of HWP1 in systemic candidiasis by use of Candida albicans strains with selectable marker URA3 targeted to the ENO1 locus.Infect. Immun.70:3281– 3283.